This proposal will test the hypothesis that insulin resistance, present universally in NIDDM patients and in up to 25% of subjects with normal glucose tolerance, may be the underlying metabolic defect resulting in low HDL levels. Reduced responsiveness of adipose tissue lipoprotein lipase to insulin and increased catabolic rate of apolipoprotein A-1 may explain low HDL-cholesterol levels in NIDDM patients and insulin resistant subjects.